Dendritic cells are professional antigen presenting cells (APCs), and play an important role in immune induction and immune regulation in a body.
The dendritic cells in a human body are only 0.3% of total white blood cells, but are immune cells capable of activating naive T cells that have never contacted antigens to induce a primary immune response, and to induce an antigen-specific acquired memory immune. The reason in which the dendritic cells are able to serve as the professional antigen presenting cells is that co-stimulatory molecules such as CD80 and CD86 and adhesion molecules such as ICAM-1 in addition to major histocompatibility complex (MHC) I/II are highly expressed on a cell surface, and various cytokines (interferon, IL-12, IL-18, etc.) related to T cell activation are secreted in a large amount.
As described above, since the dendritic cells are able to effectively induce or regulate antigen-specific T cell activity, a possibility in which the dendritic cells are used as a therapeutic agent for cancer or intractable immune diseases has been studied for a long time. It was found that when the dendritic cells directly separated from tissue or blood or dendritic cells differentiated from monocytes are sensitized with an antigen and matured dendritic cells are injected back into the body, it induces a professional antigen-specific cytotoxic T lymphocyte (CTL), and thus, a possibility of developing the dendritic cells as a vaccine for treatment of cancer or infectious diseases has been studied for a long time (Inaba, K. et al., 3. Exp. Med., 178:479, 1993; Inaba, K. et al., Int. Rev. Immunol., 6:197, 1990; Hsu, F. et al., Nature Med., 2:52, 1996).
Based on these early study results, clinical studies of dendritic cell therapy for cancer treatment have been actively conducted all over the world, and results have been reported in various carcinomas. However, clinical effects with a single therapy are less than the initial expectation.
The known reason why the dendritic cell therapy has not been successful yet is due to low immunogenicity of tumor cells and immunosuppressive substances secreted by cancer cells. In this case, if the dendritic cells are able to induce more professional anti-cancer immunity to overcome low immunogenicity of tumor cells and to induce anti-cancer immunity that is able to surpass an immunosuppressive ability of the tumor cells, therapeutic effects may be greatly improved. Under these circumstances, present inventors found that when the dendritic cells at a maturation stage rather than an immature stage were sensitized with a recombinant antigen in which an antigen is bonded with a functional peptide having a cell membrane permeability such as cytoplasmic transduction peptide [CTP: Kim, D. et al. Exp Cell Res. 312(8):1277-88, 2006], it was possible to prepare dendritic cells having remarkably improved lymph node migration ability, T cell proliferation ability, cytotoxic T lymphocyte induction ability, etc., than those of conventional dendritic cells, and confirmed that it was possible to provide an immunotherapeutic agent thereof using the same, and a pharmaceutical composition for preventing or treating tumors using the same, and completed the present invention.